Total lymphoid irradiation (TLI), a routine and safe treatment for Hodgkin's disease, produces profound and long-lasting alterations in T cell numbers and function in man. Animal studies have shown that TLI can induce specific tissue transplantation tolerance in mice and rats allowing for permanent organ graft survival. Long-term organ and marrow allograft survival has also been obtained in mongrel dogs. The goal of this proposal is to determine whether TLI is an effective and safe treatment which is superior to conventional immunosuppressive modalities in the prevention of cadaver renal allograft rejection in man. The cellular basis of the long-term immunosuppressive and tolerogenic properties of TLI will be investigated in both patients and laboratory animals in order to evolve optimum radiotherapy protocols and elucidate underlying mechanisms of regulation of transplantation immunity. In particular, we will examine the changes in the function and cell surface markers of T lymphocyte subpopulations (most importantly suppressor cells) induced by TLI, using monoclonal antibodies and the fluorescence activated cell sorter (FACS).